AMG 110, a bispecific T cell engager (BiTE) antibody construct, induces T cell mediated cancer cell death by cross-linking epithelial cell adhesion molecule (EpCAM) on tumor cells with a cluster of differentiation 3 ϵ (CD3ϵ) on T cells. We labeled AMG 110 with 89Zr or nearinfrared fluorescent dye (IRDye) 800CW to study its tumor targeting and tissue distribution. Methods: Biodistribution and tumor uptake of 89Zr-AMG 110 was studied up to 6 d after intravenous administration to nude BALB/c mice bearing high EpCAM-expressing HT-29 colorectal cancer xenografts. Tumor uptake of 89Zr-AMG 110 was compared with uptake in head and neck squamous cell cancer FaDu (intermediate EpCAM) and promyelocytic leukemia HL60 (EpCAM-negative) xenografts. Intratumoral distribution in HT-29 tumors was studied using 800CW-AMG 110. Results: Tumor uptake of 89Zr-AMG 110 can be clearly visualized using small-animal PET imaging up to 72 h after injection. The highest tumor uptake of 89Zr-AMG 110 at the 40- g dose level was observed at 6 and 24 h (respectively, 5.35 0.22 and 5.30 0.20 percentage injected dose per gram; n 5 3 and 4). Tumor uptake of 89Zr-AMG 110 was EpCAM-specific and correlated with EpCAM expression. 800CW-AMG 110 accumulated at the tumor cell surface in viable EpCAM-expressing tumor tissue. Conclusion: PET and fluorescent imaging provided real-time information about AMG 110 distribution and tumor uptake in vivo. Our data support using 89Zr and IRDye 800CW to evaluate tumor and tissue uptake kinetics of bispecific T cell engager antibody constructs in preclinical and clinical settings. 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
CITATION STYLE
Warnders, F. J., Waaijer, S. J. H., Pool, M., De Hooge, M. N. L., Friedrich, M., Van Scheltinga, A. G. T. T., … De Vries, E. G. E. (2016). Biodistribution and PET imaging of labeled bispecific T cell engaging antibody targeting EpCAM. Journal of Nuclear Medicine, 57(5), 812–817. https://doi.org/10.2967/jnumed.115.168153
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